125 Summarized discussion and future perspectives. survival than cardiac dose and toxicity. Interaction of pulmonary and cardiac toxicity has been shown to be another factor to take into account[24,25]. Furthermore, in more recent literature a correlation was found of different radiation techniques or prescribed dose and the development of lymphopenia in EC patients[26,27]. Lymphopenia is on its turn related to local tumour control as well as overall survival in this patient group [28]. The later could also explain the relatively poor response rates in the chemoradiotherapy arm of the ESOPEC study. We are curiously awaiting on the final paper, in which we hope to get more details on the radiotherapy protocol and the given dose to relevant organs at risk, such as the heart. Use of substructures in NTCP modelling In contrast to the past, where the mean heart dose was used in the NTCP modelling, nowadays, cardiac substructures are commonly used in finding associations between cardiac toxicities and dose distributions. Using these substructures has advantages as shown in papers were associations between radiation dose and cardiac substructures were generally stronger compared to associations with the mean heart dose. This can be explained by the fact that dose distributions in the heart are not homogeneous and that certain subregions of the heart can be more susceptible for certain radiation-induced complications. The highest dose is being given to tissues that are located next to the target volume. The mean dose to the heart is often not representative for the dose to this subregion of the heart which receives the highest dose. In our population of oesophageal cancer patients, the highest mean dose is given to the left atrium, closely followed by the dose to the left ventricle and the right atrium, while the right ventricle received a relatively low dose. Cardiac dose distributions in EC patients are quite different from those in breast cancer patients This, and differences in cardiovascular risk profiles, can explain the difference in cardiac toxicities seen after treating these different thoracic indications for radiotherapy. 8
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